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|Title:||Transgenic Mouse Brains for Evaluation and Quality Control of BSE Tests|
|Authors:||PHILIPP Wolfgang; GROTH Darlene; GILES Kurt; VODRAZKA Pavel; SCHIMMEL HEINZ; FEYSSAGUET Muriel; TOOMIK Reet; SCHACHER Pascal; OSMAN Awad A.; LACHMANN Ingolf; WEAR A.; ARSAC Jean-Noel; PRUSINER Stanley B.|
|Citation:||BIOLOGICAL CHEMISTRY vol. 388 no. 3 p. 349-354|
|Publisher:||WALTER DE GRUYTER \& CO|
|Type:||Articles in periodicals and books|
|Abstract:||Rapid tests for the postmortem diagnosis of bovine spongiform encephalopathy (BSE) or "mad cow disease" are one of the most widely used diagnostics in veterinary medicine. In the European Union, these rapid BSE tests were evaluated for use by the European Commission's (EC) Institute for Reference Materials and Measurements, which has resulted in 12 different officially approved tests 1,2. The continuing evaluation of new rapid tests for BSE prions and the quality control of approved BSE tests pose a challenge due to the scarcity of BSE-infected bovine brainstems and the regional variations in prion titre 3. Transgenic mice expressing bovine prion protein, designated Tg(BoPrP+/+)4092/Prnp0/0 mice 4, or Tg4092 mice for simplicity, offer an alternative approach to these problems. To determine whether BSE-infected Tg4092 mouse brains could serve as the general standard for a rapid BSE test, we inoculated Tg4092 mice intracerebrally with BSE prions, harvested their brains at defined time-points postinfection (p.i.) and analysed the cerebral hemispheres with five different rapid BSE tests. We found that such samples are generally suitable for assessing rapid BSE tests, and that de novo formation of the disease-causing prion protein isoform, designated PrPSc, can be monitored during the course of infection. All five rapid BSE tests initially detected nascent PrPSc insamples from mice as early as 21 to 49 days postinfection (d.p.i.). The rapid rise in brain PrPSc between days 49 and 98 d.p.i. was detected by all five tests; moreover, all five tests reached saturation in the detection of PrPSc between 147 and 220 d.p.i. These results demonstrate that BSE-infected Tg4092 mouse brains provide a renewable and controllable source of reference samples. Our findings suggest that BSE-infected Tg4092 mouse brains can be used for the assessment of rapid BSE test performance and quality control as well as standardization of secondary reference materials.|
|JRC Institute:||Institute for Reference Materials and Measurements|
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